# Circulating Endothelial Cells and Microvesicles as Biomarkers for Gene Therapy in Sickle Cell Disease

> **NIH NIH OT2** · UNIVERSITY OF MINNESOTA · 2020 · $300,000

## Abstract

Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide, resulting
from a mutation in the β-globin gene. The polymerization of hemoglobin S in SCD has significant
pathophysiological consequences -- hemolysis, inflammation, oxidative stress, hypercoagulability and painful
vaso-occlusive crises that promote endothelial and vascular dysfunction.
The SCD vasculature reflects the endothelial/vascular dysfunction with an active, pro-inflammatory,
procoagulant phenotype (1), increasing the number of circulating endothelial cells (CECs) and microvesicles
(MVs) . Increased number and activation status of CECs and endothelial-derived MVs (EMVs) is accompanied
by heightened expression of soluble adhesion molecules and coagulation markers. Additionally, since CECs
and EMVs compositional change reflects the activation state of their endothelial cell origin, they are emerging
as indicators of endothelial dysfunction (2-5). Previous studies have found that plasma CECs, MVs, soluble
adhesion molecules, and coagulation factors are present at low levels in healthy subjects, but are elevated in a
variety of systemic inflammatory diseases, including SCD (2, 3, 6-9). Therefore, CECs and EMVs are ideal
biomarkers for diagnosis and prognosis of inflammatory disorders, giving them huge potential in diagnosing
SCD severity. Standardizing and validating CECs and EMVs as biomarkers of disease modification aligns with
the goals of the Cure Sickle Cell Initiative, providing a defined scientific methodology to track changes in the
vascular endothelium following curative gene SCD therapy.

## Key facts

- **NIH application ID:** 10112368
- **Project number:** 3OT2HL152758-01S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JOHN D BELCHER
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,000
- **Award type:** 3
- **Project period:** 2019-09-20 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112368

## Citation

> US National Institutes of Health, RePORTER application 10112368, Circulating Endothelial Cells and Microvesicles as Biomarkers for Gene Therapy in Sickle Cell Disease (3OT2HL152758-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112368. Licensed CC0.

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